Biol. Sci., California State University, Long Beach, Long Beach, CA, USA.
Horm Behav. 2013 Jun;64(1):136-43. doi: 10.1016/j.yhbeh.2013.06.001. Epub 2013 Jun 10.
Estradiol rapidly activates a microcircuit in the arcuate nucleus of the hypothalamus (ARH) that is needed for maximal female sexual receptivity. Membrane estrogen receptor-α complexes with and signals through the metabotropic glutamate receptor-1a stimulating NPY release within the ARH activating proopiomelanocortin (POMC) neurons. These POMC neurons project to the medial preoptic nucleus (MPN) and release β-endorphin. Estradiol treatment induces activation/internalization of MPN μ-opioid receptors (MOR) to inhibit lordosis. Estradiol membrane action modulates ARH gamma-aminobutyric acid receptor-B (GABAB) activity. We tested the hypothesis that ARH GABAB receptors mediate estradiol-induced MOR activation and facilitation of sexual receptivity. Double-label immunohistochemistry revealed expression of GABAB receptors in NPY, ERα and POMC expressing ARH neurons. Approximately 70% of POMC neurons expressed GABAB receptors. Because estradiol initially activates an inhibitory circuit and maintains activation of this circuit, the effects of blocking GABAB receptors were evaluated before estradiol benzoate (EB) treatment and after at the time of lordosis testing. Bilateral infusions of the GABAB receptor antagonist, CGP52432, into the ARH prior to EB treatment of ovariectomized rats prevented estradiol-induced activation/internalization of MPN MOR, and the rats remained unreceptive. However, in EB-treated rats, bilateral CGP52432 infusions 30 min before behavior testing attenuated MOR internalization and facilitated lordosis. These results indicated that GABAB receptors were located within the lordosis-regulating ARH microcircuit and are necessary for activation and maintenance of the estradiol inhibition of lordosis behavior. Although GABAB receptors positively influence estradiol signaling, they negatively regulate lordosis behavior since GABAB activity maintains the estradiol-induced inhibition.
雌二醇迅速激活下丘脑弓状核（ARH）中的一个微电路，该微电路对于最大程度的雌性性接受性是必需的。膜雌激素受体-α与代谢型谷氨酸受体-1a 复合物并通过其信号传导，刺激 ARH 内的 NPY 释放，从而激活前阿黑皮素原（POMC）神经元。这些 POMC 神经元投射到内侧视前核（MPN）并释放β-内啡肽。雌二醇处理诱导 MPN μ-阿片受体（MOR）的激活/内化，以抑制弓状背屈。雌二醇膜作用调节 ARH γ-氨基丁酸受体-B（GABAB）活性。我们检验了假设，即 ARH GABAB 受体介导雌二醇诱导的 MOR 激活和促进性接受性。双重标记免疫组织化学显示，GABAB 受体在表达 NPY、ERα 和 POMC 的 ARH 神经元中表达。大约 70%的 POMC 神经元表达 GABAB 受体。因为雌二醇最初激活抑制性回路并维持该回路的激活，所以在雌二醇苯甲酸酯（EB）处理之前和弓状背屈测试时评估了阻断 GABAB 受体的效果。双侧将 GABAB 受体拮抗剂 CGP52432 输注到 ARH 中，可防止去卵巢大鼠 EB 处理后 MPN MOR 的雌二醇诱导的激活/内化，并且大鼠仍然不接受。但是，在 EB 处理的大鼠中，在行为测试前 30 分钟双侧 CGP52432 输注可减轻 MOR 的内化并促进弓状背屈。这些结果表明，GABAB 受体位于调节弓状背屈的 ARH 微电路内，并且是激活和维持雌二醇抑制弓状背屈行为所必需的。尽管 GABAB 受体对雌二醇信号具有正向影响，但它们负调节弓状背屈行为，因为 GABAB 活性维持雌二醇诱导的抑制。
